Neuroprotective effect of lurasidone via antagonist activities on histamine in a rat model of cranial nerve involvement

Abstract

Cranial nerve involvement frequently involves neuron damage and often leads to psychiatric disorder caused by multiple inducements. Lurasidone is a novel antipsychotic agent approved for the treatment of cranial nerve involvement and a number of mental health conditions in several countries. In the present study, the neuroprotective effect of lurasidone by antagonist activities on histamine was investigated in a rat model of cranial nerve involvement. The antagonist activities of lurasidone on serotonin 5‑HT7, serotonin 5‑HT2A, serotonin 5‑HT1A and serotonin 5‑HT6 were analyzed, and the preclinical therapeutic effects of lurasidone were examined in a rat model of cranial nerve involvement. The safety, maximum tolerated dose (MTD) and preliminary antitumor activity of lurasidone were also assessed in the cranial nerve involvement model. The therapeutic dose of lurasidone was 0.32 mg once daily, administered continuously in 14‑day cycles. The results of the present study found that the preclinical prescriptions induced positive behavioral responses following treatment with lurasidone. The MTD was identified as a once daily administration of 0.32 mg lurasidone. Long‑term treatment with lurasidone for cranial nerve involvement was shown to improve the therapeutic effects and reduce anxiety in the experimental rats. In addition, treatment with lurasidone did not affect body weight. The expression of the language competence protein, Forkhead‑BOX P2, was increased, and the levels of neuroprotective SxIP motif and microtubule end‑binding protein were increased in the hippocampal cells of rats with cranial nerve involvement treated with lurasidone. Lurasidone therapy reinforced memory capability and decreased anxiety. Taken together, lurasidone treatment appeared to protect against language disturbances associated with negative and cognitive impairment in the rat model of cranial nerve involvement, providing a basis for its use in the clinical treatment of patients with cranial nerve involvement.

Valuable interaction with cognitive remediation and optimal antipsychotics for recovery in schizophrenia (VICTORY-S): study protocol for an interventional, open-label, randomized comparison of combined treatment with cognitive remediation and lurasidone or paliperidone

“…For those reasons, the previous study was not able to assess whether lurasidone enhances the therapeutic effects of cognitive remediation. Given the reported beneficial effects of lurasidone on cognitive function (25)(26)(27)(28)(29), we hypothesize that the lurasidone plus NEAR combination group may experience a greater improvement in cognitive and social function than the paliperidone combination group. VICTORY-S is the first study to examine the potential of lurasidone to facilitate the therapeutic effects of cognitive remediation for schizophrenia.…”

“…The atypical antipsychotic drug lurasidone is a novel benzisothiazole derivative that exhibits a high binding affinity and antagonistic effect on the dopamine D 2 , serotonin (5-HT) 2A and 5-HT 7 receptors, a partial agonistic effect on the 5-HT 1A receptor, and no significant binding to histamine 1 and muscarinic acetylcholine receptors (24). In animal models, lurasidone treatment was associated with neuroprotective effects and better cognitive improvement compared with other antipsychotics (25,26). Furthermore, results from a clinical study suggest that lurasidone may improve cognitive function in patients with schizophrenia (27).…”

Psychotropics and Neuroprotection: Literature Review and Case Series Report

“…More studies are needed to see if Olanzapine and aripiprazole offers the best neuroprotection followed by quetiapine, paliperidone, Risperidone and Ziprasidone. Newer agents Asenapine, lurasidone, Brexpiprazole, and cariprazine are also reported to offer neuroprotection [36][37][38]. Lurasidone, Brexpiprazole, and cariprazine are newer agents and their efficacy in agitation management needs more evidence.…”

Factors associated with increased risk of lurasidone-induced somnolence: Two case-control studies based on one bioequivalence trial in healthy volunteers

“…In addition to its principal antagonistic activity against dopamine D2 and serotonin 5-HT2A receptors, lurasidone also exerts antagonistic activity against 5-HT7. It exhibits partial agonism for 5-HT1A receptors and modest antagonism for noradrenergic a2A and a2C receptors [ 5 ] but no affinity for histamine H1 or acetylcholine M1 receptors due to its unique chemical structure [ 6 ]. Based on its pharmacological profile, lurasidone is associated with fewer extra-pyramidal symptoms than conventional agents and effectively ameliorates various schizophrenic symptoms [ 5 , 7 ].…”